Background: Male spouses and partners play an important role in determining a woman's willingness to participate in cervical cancer screening. However, the attitudes and behaviors by which they influence a woman's decision to undergo Pap testing remain poorly understood. Methods: A series of semi-structured, qualitative interviews were conducted in Spanish with 19 recent Latino immigrants in Houston, Texas. The interview format was designed to establish each individual's pattern of engagement with the United States healthcare system, assess baseline knowledge of cervical cancer screening and evaluate attitudes and patterns of communication with their female partners regarding health care. Interview questions were constructed using principles of the Theory of Reasoned Action. All interviews were conducted in Spanish. After translation, responses were coded and scored with the goal of identifying themes and key observations. Results: Most subjects reported few, if any, interactions with the healthcare system since their arrival in the United States. Although most participants reported being aware that women should be seen by their doctors regularly, fewer than half could clearly indicate the purpose of a Pap test or could state with certainty the last time their female partner had undergone screening. Multiple subjects expressed a general distrust of the health care system and concern for its costs. Approximately half of subjects reported that they accompanied their female partner to the health care provider's office and none of the participants reported that they were present in examination rooms at the time their partner underwent screening. Multiple participants endorsed that there may be some concerns within their community regarding women receiving frequent gynecologic care and distrust of the healthcare system. Almost all interviewed subjects stated that while they would allow their female partners to see male physicians, they also expressed the opinion that other men might be uncomfortable with this and that women would likely be more comfortable with female physicians.

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Paired Box 8 (PAX8) is a transcription factor clinically utilized as a histologic biomarker for cancers arising in tissues derived from the embryonic Mullerian tract. Although dysregulated PAX8 expression has recently been shown to promote the growth of ovarian and renal cancers, its role in uterine cancer remains poorly understood. Here, we hypothesized that overexpression of PAX8 promotes uterine cancer growth and metastasis. When 108 uterine cancer specimens were evaluated by mass spectroscopy, the highest levels of PAX8 were found in TP53-mutated, copy number (CN)-high specimens. In vitro, we found that targeting PAX8 expression resulted in decreased rates of both proliferation and apoptosis in multiple representative cell lines (ARK2 and ARK4). PAX8 knockdown also negatively impacted rates of in vitro migration and invasion assessed using commercially available Boyden chamber assays. Using whole-exome and transcriptomic profiling performed by Next Generation Sequencing, we found that PAX8 knockdown resulted in increased expression of 268 gene products by >1.5-fold, and decreased expression of 179 gene products (adj p<0.01; FDR<1%). Specific gene products whose expression was altered by targeting PAX8 expression included IL-1β, IL-11, and MUC1. With qPCR, we confirmed that levels of IL-1β were 13.8-fold and 3.4-fold higher in cultures of ARK2 and ARK4 cells transfected with PAX8-specific siRNA, respectively, when compared to cultures transfected with a nontargeting control (p<0.01). Using these transfections, we also confirmed increased expression of IL-11 in ARK2 cells (RQ=3.22, p<0.01) and ARK4 cells (RQ = 2.28, p<0.01), and increased expression of MUC1 in ARK2 cells (RQ=1.13, p<0.01). Collectively, our findings demonstrate that PAX8 regulates the proliferation of CN-high uterine cancers, potentially through the regulation of IL-1β expression. Notably, our data also implicates PAX8 expression as a key mediator of the inflammatory response to these aggressive cancers. Key differences in PAX8’s relationship with proliferation and these select few signaling molecules, compared to what is seen in other PAX8-dependent cancers, suggest unique roles for PAX8 as an oncogene in uterine cancers. Citation Format: Lauren Karnolt, Maja Okuka, Susan Read, Yongchao Dou, Bing Zhang, Thomas J. Rutherford, Matthew L. Anderson. The role of PAX8 in copy number-high uterine cancers: Inflammatory cytokine modulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1317.

Background: Little is known about the influence of smoking on ovarian cancer survival. We investigated this relationship in a hospital-based study. Methods: Analyses included 519 women with ovarian cancer. We used multivariable adjusted Cox proportional hazards regression models to estimate HRs and 95% confidence intervals (CI). Results: Risk of all-cause mortality was increased for current smokers (HR = 1.70; 95% CI: 1.09–2.63) versus never smokers, especially for those with ≥15 cigarettes per day (HR = 1.92; 95% CI: 1.15–3.20). Results were largely similar after additional adjustment for debulking status (current vs. never smokers, HR = 2.96; 95% CI: 1.07–8.21) or neoadjuvant chemotherapy (comparable HR = 2.87; 95% CI: 1.02–8.06). Compared with never smokers, smoking duration ≥20 years (HR = 1.38; 95% CI: 0.94–2.03) and ≥20 pack-years (HR = 1.35; 95% CI: 0.92–1.99) were suggestively associated with worse outcomes. Current smoking was also positively associated with the risk of mortality among patients with ovarian cancer recurrence (current vs. never/past smokers, HR = 2.79; 95% CI: 1.44–5.41), despite the null association between smoking and recurrence (HR = 1.46; 95% CI: 0.86–2.48). Furthermore, no association was observed for smoking initiation before age 18 (HR = 1.22; 95% CI: 0.80–1.85), or either environmental smoke exposure at home (HR = 1.16; 95% CI: 0.76–1.78) or at work (HR = 1.10; 95% CI: 0.75–1.60). Conclusions: Our results suggest active tobacco smoking is associated with worse ovarian cancer outcomes, particularly after a recurrence. Impact: Our findings support structured smoking cessation programs for patients with ovarian cancer, especially in recurrent settings. Further research to confirm these findings and examine the interplay between smoking and the tumor immune microenvironment may help provide insight into ovarian cancer etiology.